PROJECT SUMMARY The main goal of the Dystonia Coalition is to provide the foundations necessary for the development and evaluation of novel treatments for the isolated dystonias, previously known as ?primary? dystonias. The most common subtypes include cervical dystonia (also known as torticollis), blepharospasm and related craniofacial dystonias (sometimes called Meige syndrome), laryngeal dystonia (also known as spasmodic dysphonia), and limb dystonias (e.g., writer?s cramp, musician?s dystonias, foot dystonia). Also included are various combinations such as segmental and multifocal dystonias, and less common generalized dystonias affecting broader areas the body. Although there have been dramatic advances in understanding the basic biology of dystonia, they have not yet been translated into effective treatments for patients. The development of new treatments has been hampered by incomplete knowledge regarding the natural history of these disorders and variations in responses to existing therapies, a lack of objective tools to monitor severity, and the absence of useful biomarkers. The Dystonia Coalition has made great progress in addressing many translational barriers during prior funding cycles. The current renewal application leverages this success and targets ongoing challenges in the translational effort. It is organized into Administrative Unit, a Pilot Projects Program, a Career Enhancement Program, and four Clinical Research Projects. The Clinical Research Projects each focus on key unmet needs in the development of new therapies. Project 1 is a natural history study of all subtypes of isolated dystonias, and acts as a repository for distribution of data to investigators. This project provides essential baseline data for any novel therapy that proposes to reduce progression. Project 2 addresses individual and temporal variations in response to existing therapy with botulinum toxin. Because these treatments are standard of care for many types of dystonia, delineating these sources of variation provides baseline data essential for any novel add-on therapy that proposes to mitigate symptoms. Project 3 focuses on the development of novel technologies as objective tools for assessing the severity of the most common subtypes of dystonia. These tools are valuable outcome measures for clinical trials. Project 4 functions as a centralized biorepository resource for collection of biomaterials for all subtypes of dystonia and implements preliminary studies of potential relevant biomarkers. These materials may then be used to explore potential diagnostic and severity biomarkers for different types of dystonia. To facilitate rapid recruitment for all of these projects and to encourage collaboration, the Dystonia Coalition has maintained a unique open-door policy that permits qualified centers to contribute to specific projects according to their special interests and abilities. During prior funding cycles, the Dystonia Coalition started with 14 sites but ultimately engaged 49 sites to conduct the various projects across North America, Europe, Israel, and Australia. Dystonia Patient Advocacy Groups participate in all of these activities at multiple levels.